DESCRIPTION (adapted from the application) Acute liver failure is a rare condition in which liver cell damage occurs rapidly leading to severe multi-organ failure requiring high resource utilization and, frequently, a fatal outcome. Prior to 1997, little research had been performed in the US regarding this condition because of the lack of a multi-center mechanism to study this rare disease or to perform therapeutic trials. The Acute Liver Failure Study Group was developed to answer this need. Tissue and serum samples as well as detailed epidemiologic and clinical data have been collected since January 1, 1998, at 14 sites around the US. Our results suggest that 50% of acute liver failure in the US is currently due to toxicity of pharmaceutical agents, both prescription and non-prescription drugs. Data concerning the use of transplantation and the outcome of ALF are now available. Existing scoring systems used to determine the need for liver transplantation have been tested in the patient group. Serum samples have been analyzed for new prognostic indicators and to identify possible candidate viruses in those for whom a causal agent cannot be identified. We also initiated a pilot study of the use of N-acetylcysteine for the treatment of ALF not caused by acetaminophen. Thus, the group has already provided several new insights into this condition, and has put in motion the mechanism for conducting controlled, blinded, and randomized studies of this important condition. The present proposal is to extend the study for an additional four years, plus one additional year for data analysis, and to expand the ALF Study Group to include 21 adult centers, while adding pediatric patients at 18 sites. Our current aims are similar to our previous ones: to gather further important clinical data and specimens for analysis and study, and to continue the N-acetylcysteine trial to its completion. The overall goal is to apply modern clinical, epidemiological and virological techniques to the study of this rare but devastating illness.